OBJECTIVE To examine the changes in the release pattern of GH with aging. A decline in somatic function in association with aging has been correlated with a decrease in growth hormone (GH) release. To understand neuroendocrine contributions to age-related changes in GH release, we conducted 2 experiments in aged and young adult female rhesus monkeys. In Study 1, we assessed circulatory GH levels in 5 aged (average 26.3 yr) and 7 young (average 5.4 yr) monkeys by collecting serum samples every 10 min (1600 h to 0200 h) through an indwelling catheter, and measuring GH levels by RIA. Results were analyzed using the PULSAR algorithm. Mean GH release in aged monkeys was significantly (p<0.05) lower than in young adults. Pulse amplitude was also significantly (p<0.05) lower in aged than young monkeys, whereas interpulse interval was not different between age groups. In Study 2, we examined the effects of iv injection of 1) GH-releasing hormone (GHRH, 1 5g/kg), 2) GHRP-2 (1 5g/kg), and 3) a combination of GHRH and GHRP-2 (both 1 5g/kg) on GH release in 4 young and 3 aged female monkeys. After 1 h of control sampling, each challenge was sequentially given at 2.5 h intervals, while serum samples were continuously collected at 15-min intervals. The response to peptide challenge was calculated as the change in GH level from the average of the 2 pre-challenge values (30 min). In aged and young monkeys, both GHRH alone and GHRP-2 alone induced GH release. The GHRH and GHRP-2 combination challenge resulted in synergistic effects on GH release (5-6 fold increase in GH over the value induced by either GHRH or GHRP-2 alone) in young adults, whereas no synergistic effects were observed in aged monkeys. These data suggest the decline of GH release in aged monkeys (Study 1), may be due to an impairment of the mechanism involved in the synergistic action between GHRH and GHRP-2 on GH release in aged monkeys (Study 2). FUTURE DIRECTIONS We will measure release of GHRH and somatostatin in the stalk-median eminence during aging. KEY WORDS growth hormone (GH), aging, pulsatile release of GH, GHRH, GHRP FUNDING NIH AG14972, & RR00167